Will Scientists Figure Out How to Protect Us from Radiation?

Researchers might have found a way to protect cells from radiation damage.

In a study published in the new [American Association for the Advancement of Science] journal Science Translational Medicine [here’s the study; the prestigious journal Nature also commented on the study], researchers at the University of Pittsburgh School of Medicine and the National Cancer Institute found that they could protect healthy cells from radiation injury by turning off an inhibitory pathway that regulates nitric oxide.

“[Nitric oxide] is a bio gas, produced by enzymes in cells, and flies around almost at light speed compared to other processes,” Jeff Isenberg, M.D., a professor at Pitt’s school of medicine, tells DOTmed News.

While nitric oxide mostly works to prevent clotting of arteries, it also appears to help animals survive stress conditions.

But Dr. Isenberg and his team made the discovery that by switching off a related inhibitory pathway that controls nitric oxide, they could give animals “near immunity to record levels of radiation,” he says.

In mice, when Dr. Isenberg and his team introduced a drug that prevented a protein, thrombospondin-1, from binding to a surface cell receptor called CD47, the animals could endure almost unheard-of doses of radiation with virtually no ill effects.

In cellular studies, cells could withstand up to the tested amount: 60 Gy. And in whole animal studies, mice could endure the limit they were given: 40 Gy.

40 Gy is a much higher level of radiation than is normally used in studies.

Shockingly, the irradiated rodents were almost completely unharmed. Other than some mild hair loss at the site of dosage, there was almost no cell death or damage when histological samples were checked.

“There was no skin laceration or muscle loss,” Dr. Isenberg says. “When we stained for cell death, we didn’t even see significant loss of bone marrow, which is exquisitely sensitive…to radiation damage.”

In comparison, control mice — who didn’t get the pathway-blocking treatment — were eaten away with tissue loss and “frank necrosis of the limbs.”

***

Currently, his lab is working toward getting funds for toxicology tests so at some point drugs could be developed for humans. He also plans studies to see how long an effective dose lasts — would someone get one-month, or one-year immunity following a dose?

Also, a bigger mystery is figuring out how, by blocking this pathway, cells are able to fix the damaged DNA within. Dr. Isenberg says they know that following radiation exposure, the DNA is scrambled, but somehow, with this treatment, the cells are able to get themselves right.

“It’s not that we’re blocking radiation from hitting the tissue,” he says. “Somehow…they repair themselves, and go about their business.”

This treatment is not a cure-all. Specifically, high doses of radiation would like cause damage through over-heating our cells:

At some point radiation would damage tissue through thermal energy, which this process might not be able to stop.

And scientists don’t yet know whether or not this treatment might have harmful long-term side effects:

Research may reveal why we aren’t born with the inhibitory pathway already blocked. Dr. Isenberg says the process probably evolved when deep sea fishes emerged on land, and somehow was used to regulate changes in internal pressure. So would turning it off create other, unwanted effects? Although none were seen in the studies, nitric oxide is a powerful vasodilator, he says, and maybe the body needs some way to control it.

Three of the authors of the study – including David Roberts of the Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health – have published threefollow-up studies in 2012 and 2013 confirming the radioprotective benefits of their approach.

Washington’s Blog contacted Dr. Roberts and asked him to explain what the new studies show, and whether any adverse side effects have been seen since 2009. Dr. Roberts told us:

Our second published study … demonstrates that mice can be protected from lethal total body irradiation by using the same antisense approach to suppress CD47 that we employed in the 2009 … paper. This includes protection against the hematopoietic syndrome and the gastrointestinal syndrome that are responsible for most deaths caused by lethal total body irradiation. No side effects were seen.

And It Kills Tumor Cells …

But won’t this treatment protect cancerous cells from radiation treatment?

No … it actually attacks the tumor cells. As Science Direct reported in 2009:

Researchers at the University of Pittsburgh School of Medicine and the National Cancer Institute (NCI), part of the National Institutes of Health, may be hot on the heels of a Holy Grail of cancer therapy: They have found a way to not only protect healthy tissue from the toxic effects of radiation treatment, but also increase tumor death.

***

There have been concerns that approaches to spare healthy cells will risk inadvertently protecting tumor cells, noted senior author David D. Roberts, Ph.D., of the NCI’s Center for Cancer Research. But, he added, “in our experiments, suppression of CD47 robustly delayed the regrowth of tumors in radiation-treated mice.”

Indeed, a number of studies by other researchers have found that increased nitric oxide makes tumor cells with lower-than-normal oxygen levels more vulnerable to radiation. See this, this and this. (Tumor cells have low oxygen levels whenever tumors get too big to support the vasculature – i.e. blood-carrying system – which transports oxygen to cells.)

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of political, economic, scientific, and educational issues. We believe this constitutes a 'fair use' of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes. For more information go to: